Lung cancer increases in non-smoking women baffle scientists

Though she was never a smoker, Erickson is one of a growing number of American women who are being diagnosed with lung cancer. Scientists aren’t sure why women have higher lung cancer risk, but they are searching for clues while new treatments are helping those battling the disease live longer.

“Lung cancer in younger, never-smoking females is on the rise,” said Dr. Ticiana Leal, director of the Thoracic Medical Oncology Program at Emory’s Winship Cancer Institute. “This is noteworthy because symptoms of lung cancer otherwise can be overlooked in young never-smoking females and can go unrecognized, which leads to delayed diagnoses with detrimental impact on survival.”

The research into lung cancer in women has taken on a new urgency as data has revealed that 20% of lung cancer diagnoses in the U.S. now happen in those who have never smoked. And never-smokers who develop lung cancer are nearly twice as likely to be women than men, according to a team of researchers at Harvard.

According to the National Cancer Institute, in 2024, an estimated 611,720 people will die of cancer in the United States. Lung and bronchus cancer is responsible for the most deaths, accounting for 20% of all cancer deaths with 125,070 people expected to die from the disease.

Smoking-related lung cancer deaths in the United States have been decreasing 2.7% per year since 1991. But researchers haven’t determined why women who have never smoked now have higher odds of getting lung cancer than men who have never smoked. One theory suggests that women might be more prone to gene mutations that then make them more susceptible to environmental stressors that can trigger cancer.

The stressors that can trigger lung cancer in those who have never smoked are the usual suspects: outdoor and indoor air pollution, secondhand tobacco smoke, diesel exhaust, radon and asbestos, according to the CDC. A family history of lung cancer remains the most significant risk factor.

But what is causing women to undergo gene mutations that then make them more susceptible to lung cancer? And why are some mutations observed in 40% to 50% of U.S. Asian populations compared to only 10% to 15% in U.S. white populations? And how do environmental factors play a role? That’s the focus of research in the U.S. and elsewhere, said Babak Baban, a professor of immunology and associate dean for research at Augusta University.

“Genetic factors may increase the susceptibility to other risk factors in lung cancer,” Baban said. “They may make it difficult for individuals to neutralize and reject the chemicals from the environment or smoking, so the risk of getting cancer would be higher.”

Lung cancer has long been a threat to public health in the U.S., and remains the No. 1 cause of cancer death in both men and women. Experts are alarmed, however, that the incidence has not declined in U.S. women as much as it has in men over the past 20 years, despite similar rates of smoking cessation among the genders.

One recent study found that Asian American women who have never smoked are twice as likely to be diagnosed with lung cancer as white women with similar non-smoking habits; a second study showed that among Asian American women, half of whom smoked, rates have increased by 2% each year. One theory suggests that higher exposure to indoor and outdoor air pollution might be triggering the cancers.

In Erickson’s case, family history may have played a role: her aunt died of lung cancer, and immediate relatives have developed breast cancer. Still, upon receiving her diagnosis in 2016, she was surprised to learn that a non-smoker like herself could be at risk.

Though in a sense, she was lucky: her lung cancer is known as non-small cell lung cancer (NSCLC) with a mutation known as “EGFR” or epidermal growth factor receptor. EGFR is a gene that makes a protein involved in cell growth and cell survival. A mutation in this gene can cause cancer cells to grow and spread in the body.

About 80% to 85% of lung cancers in the U.S. are non-small cell, according to the American Cancer Society. A major difference between it and small-cell lung cancer (SCLC) is that non-small cell cancers spread more slowly, and respond favorably to treatment. Small-cell lung cancers spread quickly and do not generally respond to treatment, meaning life expectancy can be about four to five months, though a new drug holds promise.

Erickson’s doctor, Dr. Suresh Ramalingam at Emory, treated her lung cancer with a different drug that targets the EGFR mutation itself.

EGFR-positive lung cancer represents about 10% to 35% of lung cancer in the United States, and patients with EGFR mutation lung cancers tend to have minimal to no smoking history, according to the American Lung Association. One theory holds that EGFR mutations might be associated with a history of pneumonia and gastroesophageal reflux disease – but more research is needed to prove this.

The other lung cancer-causing mutations read like a veritable alphabet soup. The common thread among them is that the mutations weren’t inherited, but likely took place during a person’s lifetime due to exposure to a trigger, such as cigarette smoke or air pollution.

Augusta-native Stephanie Johnson, 37, has wondered for months if stress played a role in the genetic mutation responsible for her lung cancer. She didn’t have a family history of lung cancer, and had “only smoked maybe five cigarettes in college.” She sought care for bronchitis in November 2023, and was shocked by what tests revealed: bronchitis in her right lung and a cancerous tumor in her left.

Genetic testing revealed that she also had non-small cell lung cancer. She had chemotherapy in February, and surgery in May. She faces two years of treatment with a targeted oral therapy, along with scans every three months.

Dr. Daniel Miller, a thoracic surgeon who treats lung cancer at the Georgia Cancer Center of the Medical College of Georgia, says he now sees more non-small cell lung cancers in non-smoking women than men. Though he was optimistic about the treatment plan developed by a team of physicians for a possible long-term survival for Johnson, he said he is frustrated that he isn’t able to tell her and other patients why women are developing the tumor mutations that make them more susceptible to lung cancer.

“We don’t know why, yet we are seeing it everyday,” he said. “It could be related to stress on the immune system.”

Had Johnson not been diligent about asking for follow-up tests, she wouldn’t have qualified for a lung cancer screening under current guidelines, Miller said.

According to the Centers for Disease Control and Prevention, screening is recommended only for adults who have no symptoms of lung cancer, but are at high risk. The only recommended screening test for lung cancer is low-dose CT scans or computed tomography. The U.S. Preventive Services Task Force recommends annual screening for lung cancer in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.

“In Georgia, only 5% of people who are eligible for lung cancer screenings get them,” Miller said. “By the time people have symptoms, it has often spread to other organs. It’s a question of access.”

To broaden access, Miller is raising funds to create a mobile lung cancer screening unit to see patients who live within a 50- to 75-mile radius of Augusta.

Increased screenings could indeed help Georgia reduce its lung cancer rates.

According to the American Cancer Society’s 2024 report, Georgia’s lung cancer rates are higher than the national average, with an estimated 7,350 new cases this year. Georgia will be one of only six states with more new cases than the national average. High smoking rates and radon exposure in Georgia account for the higher rates, said Ahmedin Jemal, senior vice president of Surveillance & Health Equity Science at the American Cancer Society. Radon is a naturally occurring, odorless gas that increases the risk of developing lung cancer.

“In Georgia, we have an incidence rate of lung cancer that is twice as high as in Utah, and about three times as high in Georgia men compared to men in Utah,” Jemal said.

Jemal says some of the lung cancer cases occurring in never-smoking women are due to exposure to second-hand smoke given that second-hand smoke causes thousands of lung cancer deaths in the United States.

He is lobbying for increased funding for tobacco secession programs in Georgia, which he says are underfunded. “In Georgia, we are only spending 2% of the amount recommended by the CDC, compared to 100% in Maine,” he noted.

Indeed, tobacco use in Georgia remains high: 16% of GA adults smoke, compared to 24% in West Virginia, 22% in Arkansas, 9% in California, and 7% in Utah, according to the American Cancer Society.

Another mechanism to decrease smoking could be to increase the tax on cigarettes, which in Georgia is 37 cents per pack, compared to $4.50 per pack in Washington, DC. Only one state has a lower per-pack tax imposed on cigarette sales, according to the CDC. Enacting a state-wide workplace smoking ban would also help, Jemal added.

Female lung cancer survivors like Johnson and Erickson are hopeful that treatments they are receiving will keep working.

“I am grateful for these targeted therapies,” Erickson said. “As far as I know, there isn’t ‘the next pill.’ My doctor says we will ride this bus as long as we can.”

Georgia’s lung cancer stats

Sources: American Lung Association, Georgia Department of Public Health

What accounts for lung cancer in Georgia?

Source: American Lung Association